This invention relates to vehicles for topical application of medicaments. In particular, this invention relates to new, improved medicament vehicles having advantages over previously known vehicles.
One of the oldest types of medicament vehicles is the ointment; a preparation containing active medications that can be readily applied and rubbed into the skin. It serves as a means for distributing the medication uniformly over the skin surface and maintaining it there until beneficial action can occur. The earliest ointment preparations were based on fats, waxes, greases and petrolatum. These are, by nature, greasy, or not water-washable and having a limited ability to release medication to the skin. A non-aqueous ointment of more recent origin is a mixture of polyethylene glycols having molecular weights of 1,000 to 20,000. This vehicle, although water-washable, has a greasy texture and does not provide an occlusive dressing on a treated surface. Prior to this invention, these anhydrous ointment bases were the only vehicles available for medicaments which deteriorated in the presence of moisture, oxidants, and peroxides.
Emulsified creams, such as cold creams, were developed to reduce greasiness, while still maintaining the unctuousness and spreadability of the older greasy-type ointments. The emulsified creams have an aqueous base, however, and are not suitable for many drugs because their water content does not provide an appropriate milieu for optimum stability. The medicament in turn may destroy the emulsions, that is, break the emulsions and permit separation of the vehicle components.
One system which is not subject to the above disadvantages is the non-aqueous fatty alcohol-propylene glycol vehicle described in U.S. Pat. No. 3,592,930 granted to Katz et al. Another system is an improved non-aqueous vehicle with a propylene carbonate solvent system, U.S. Pat. No. 3,924,004 granted to Chang et al, as well as U.S. Pat. No. 4,017,615 granted to Shastri, et al.
A problem created by these formulae is the presence of glycol with its potential for peroxide formation. A recent study has indicated that peroxidation of the medicament vehicle may adversely affect the medicament (Implications of Peroxide Formation in Lotion and Ointment Dosage Forms Containing Polyethylene Glycols, McGinty et al. Drug Development Communications, 2(6), 505-519 (1976)).
The mechanisms of degradation may be depicted thus: ##STR1##
A markedly superior medicament vehicle would arise if the potential for peroxide formation and actual peroxide formation were severly limited.
Such vehicle should retain the properties of a non-aqeuous phase that was nevertheless unusable as to a second non-aqueous phase. This would allow substances such as corticosteroids to remain available in relatively high concentrations in one phase and not be distributed throughout the second phase. Such vehicle should form an occlusive seal as to air yet permit mobilization of aqueous soluble materials.
It is accordingly the purpose of this invention to retain the advantages of the previous non-aqeuous biphasic type ointments while avoiding the problems attendant to peroxide formation present in the prior art.
It is a further object of this invention to provide a vehicle using a particular solvent, as to topical preparations. Ethylene carbonate has exceptional solubilizing properties, particularly for corticosteroids. By combining surfactant with a petroleum wax type base, an antioxidant and propylene carbonate, a stable cream can be prepared.